A. Wallia, K. Schmidt, Diana Johnson Oakes, Teresa Pollack, N. Welsh, S. Kling-Colson, Suruchi Gupta, Candice Fulkerson, G. Aleppo, N. Parikh, J. Levitsky, JP Norvell, A. Rademaker, M. Molitch
Context: Previous studies have shown a relationship between glycemic control and posttransplant morbidity. Objective: We conducted a prospective randomized controlled trial in postliver transplant patients to evaluate intensive inpatient glycemic control and effects on outcomes to 1 year. Research Design and Intervention: A total of 164 patients [blood glucose (BG) >180 mg/dL] were randomized into 2 target groups: 82 with a BG of 140 mg/dL and 82 with a BG of 180 mg/dL. Continuous insulin infusions were initiated and then converted to subcutaneous basal bolus insulin therapy by our glucose management service. Results: The inpatient mean BG level was significantly different (140 group, 151.4 ± 19.5 mg/dL vs 180 group, 172.6 ± 27.9 mg/dL; P < 0.001). Any infection within 1 year occurred in 35 of the 82 patients (42.7%) in the 140 group and 54 of 82 (65.9%) in the 180 group (P = 0.0046). In a time-to-first infection analysis, being in the 140 group resulted in a hazard ratio of 0.54 (95% confidence interval, 0.35 to 0.83; P = 0.004); the difference between the 2 groups was statistically significant at 1 month (P = 0.008). The number with adjudicated transplant rejection was similar between the 2 groups [17 of 82 (20.7%) and 20 of 82 (24.3%) in the 140 and 180 groups, respectively; P = not significant]. Severe hypoglycemia (BG ⩽40 mg/dL) occurred in 3 patients (2 in the 140 group and 1 in the 180 group). However, more patients had moderate hypoglycemia (BG, 41 to 70 mg/dL) in the 140 group [27 of 82 (32.9%) vs 10 of 82 (12.2%) in the 180 group; P = 0.003]. Insulin-related hypoglycemia was not associated with the incidence of severe adverse outcomes. Conclusions: Glycemic control of 140 mg/dL safely resulted in a reduced incidence of infection after transplantation compared with 180 mg/dL, but with an increase in moderate hypoglycemia.
{"title":"Glycemic Control Reduces Infections in Post–Liver Transplant Patients: Results of a Prospective, Randomized Study","authors":"A. Wallia, K. Schmidt, Diana Johnson Oakes, Teresa Pollack, N. Welsh, S. Kling-Colson, Suruchi Gupta, Candice Fulkerson, G. Aleppo, N. Parikh, J. Levitsky, JP Norvell, A. Rademaker, M. Molitch","doi":"10.1210/jc.2016-3279","DOIUrl":"https://doi.org/10.1210/jc.2016-3279","url":null,"abstract":"Context: Previous studies have shown a relationship between glycemic control and posttransplant morbidity. Objective: We conducted a prospective randomized controlled trial in postliver transplant patients to evaluate intensive inpatient glycemic control and effects on outcomes to 1 year. Research Design and Intervention: A total of 164 patients [blood glucose (BG) >180 mg/dL] were randomized into 2 target groups: 82 with a BG of 140 mg/dL and 82 with a BG of 180 mg/dL. Continuous insulin infusions were initiated and then converted to subcutaneous basal bolus insulin therapy by our glucose management service. Results: The inpatient mean BG level was significantly different (140 group, 151.4 ± 19.5 mg/dL vs 180 group, 172.6 ± 27.9 mg/dL; P < 0.001). Any infection within 1 year occurred in 35 of the 82 patients (42.7%) in the 140 group and 54 of 82 (65.9%) in the 180 group (P = 0.0046). In a time-to-first infection analysis, being in the 140 group resulted in a hazard ratio of 0.54 (95% confidence interval, 0.35 to 0.83; P = 0.004); the difference between the 2 groups was statistically significant at 1 month (P = 0.008). The number with adjudicated transplant rejection was similar between the 2 groups [17 of 82 (20.7%) and 20 of 82 (24.3%) in the 140 and 180 groups, respectively; P = not significant]. Severe hypoglycemia (BG ⩽40 mg/dL) occurred in 3 patients (2 in the 140 group and 1 in the 180 group). However, more patients had moderate hypoglycemia (BG, 41 to 70 mg/dL) in the 140 group [27 of 82 (32.9%) vs 10 of 82 (12.2%) in the 180 group; P = 0.003]. Insulin-related hypoglycemia was not associated with the incidence of severe adverse outcomes. Conclusions: Glycemic control of 140 mg/dL safely resulted in a reduced incidence of infection after transplantation compared with 180 mg/dL, but with an increase in moderate hypoglycemia.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"39 1","pages":"451–459"},"PeriodicalIF":0.0,"publicationDate":"2016-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79046813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Ohlsson, D. Sundh, Andreas Wallerek, M. Nilsson, M. Karlsson, H. Johansson, D. Mellström, M. Lorentzon
Context: Areal bone mineral density (aBMD) measured using dual-energy X-ray absorptiometry (DXA) is used clinically to predict fracture but does not discriminate between trabecular and cortical bone assessment. Objective: This study aimed to investigate whether information on cortical and trabecular bone predict fracture risk independently of aBMD and clinical risk factors. Design and Participants: Cortical area, bone mass, porosity, and trabecular bone volume fraction (BVTV) were measured at the tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in 456 men (80.2 ± 3.5 years) recruited from the general population in Gothenburg, Sweden. aBMD was measured using DXA. Incident fractures (71 men) were X-ray verified. Associations were evaluated using Cox regression. Results: Cortical area [hazard ratio (HR) per standard deviation (SD) decrease, 2.05; 95% confidence interval (CI), 1.58 to 2.65], cortical bone mass (HR, 2.07; 95% CI, 1.58 to 2.70), and BVTV (HR, 1.62; 95% CI, 1.26 to 2.07), but not cortical porosity, were independently associated with fracture risk. These associations remained after adjustment for femoral neck aBMD and Fracture Risk Assessment risk factors (area: HR 1.96, 95% CI, 1.44 to 2.66; mass: HR 1.99, 95% CI, 1.45 to 2.74; BV/TV: HR 1.46, 95% CI, 1.09 to 1.96). After entering BV/TV and cortical area or bone mass simultaneously in the adjusted models, only the cortical parameters remained important predictors of fracture. Conclusion: HR-pQCT measurement of cortical area and mass might add clinically useful information for the evaluation of fracture risk.
{"title":"Cortical Bone Area Predicts Incident Fractures Independently of Areal Bone Mineral Density in Older Men","authors":"C. Ohlsson, D. Sundh, Andreas Wallerek, M. Nilsson, M. Karlsson, H. Johansson, D. Mellström, M. Lorentzon","doi":"10.1210/jc.2016-3177","DOIUrl":"https://doi.org/10.1210/jc.2016-3177","url":null,"abstract":"Context: Areal bone mineral density (aBMD) measured using dual-energy X-ray absorptiometry (DXA) is used clinically to predict fracture but does not discriminate between trabecular and cortical bone assessment. Objective: This study aimed to investigate whether information on cortical and trabecular bone predict fracture risk independently of aBMD and clinical risk factors. Design and Participants: Cortical area, bone mass, porosity, and trabecular bone volume fraction (BVTV) were measured at the tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in 456 men (80.2 ± 3.5 years) recruited from the general population in Gothenburg, Sweden. aBMD was measured using DXA. Incident fractures (71 men) were X-ray verified. Associations were evaluated using Cox regression. Results: Cortical area [hazard ratio (HR) per standard deviation (SD) decrease, 2.05; 95% confidence interval (CI), 1.58 to 2.65], cortical bone mass (HR, 2.07; 95% CI, 1.58 to 2.70), and BVTV (HR, 1.62; 95% CI, 1.26 to 2.07), but not cortical porosity, were independently associated with fracture risk. These associations remained after adjustment for femoral neck aBMD and Fracture Risk Assessment risk factors (area: HR 1.96, 95% CI, 1.44 to 2.66; mass: HR 1.99, 95% CI, 1.45 to 2.74; BV/TV: HR 1.46, 95% CI, 1.09 to 1.96). After entering BV/TV and cortical area or bone mass simultaneously in the adjusted models, only the cortical parameters remained important predictors of fracture. Conclusion: HR-pQCT measurement of cortical area and mass might add clinically useful information for the evaluation of fracture risk.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"51 1","pages":"516–524"},"PeriodicalIF":0.0,"publicationDate":"2016-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82672194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Schneider, D. de Wit, T. Links, N. V. van Erp, J. J. M. van der Hoeven, H. Gelderblom, I. Roozen, M. Bos, W. Corver, T. van Wezel, J. Smit, H. Morreau, H. Guchelaar, E. Kapiteijn
Background Mammalian target of rapamycin (mTOR) upregulation has been reported to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR inhibitor everolimus has shown promising results in endocrine tumors. We conducted a prospective phase II clinical trial to determine the efficacy and safety of everolimus in patients with advanced follicular-derived thyroid cancer. Patients and Methods Twenty-eight patients with progressive metastatic or locally advanced radioactive refractory differentiated thyroid cancer and 7 patients with anaplastic thyroid cancer were included and received everolimus 10 mg orally once daily. The primary endpoint was disease control rate [complete (CR) + partial response (PR) + stable disease (SD) > 24 weeks]. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and mutational and pharmacokinetic-related outcomes. Results Median follow-up duration was 38 months (2-64). Seventeen patients (65%) showed SD, of which 15 (58%) showed SD >24 weeks. No CR or PR was observed. Median PFS and OS were 9 [95% confidence interval (CI): 4 to 14] and 18 (95% CI: 7 to 29) months, respectively. Survival was negatively influenced by the presence of bone metastases. Toxicity was predominantly grade 1/2 and included anemia (64%), cough (64%), stomatitis (61%), and hyperglycemia (61%). Duration of SD was related to everolimus exposure. The presence of somatic gene variants related to mTOR signaling did not clearly stratify for responses. Conclusion Everolimus has clinically relevant antitumor activity in patients with advanced differentiated thyroid cancer. Given the observed disease control rate and the relatively low toxicity profile, further investigation of everolimus in sequential or combination therapy in these patients is warranted.
{"title":"Everolimus in Patients With Advanced Follicular-Derived Thyroid Cancer: Results of a Phase II Clinical Trial","authors":"T. Schneider, D. de Wit, T. Links, N. V. van Erp, J. J. M. van der Hoeven, H. Gelderblom, I. Roozen, M. Bos, W. Corver, T. van Wezel, J. Smit, H. Morreau, H. Guchelaar, E. Kapiteijn","doi":"10.1210/jc.2016-2525","DOIUrl":"https://doi.org/10.1210/jc.2016-2525","url":null,"abstract":"Background\u0000Mammalian target of rapamycin (mTOR) upregulation has been reported to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR inhibitor everolimus has shown promising results in endocrine tumors. We conducted a prospective phase II clinical trial to determine the efficacy and safety of everolimus in patients with advanced follicular-derived thyroid cancer.\u0000\u0000\u0000Patients and Methods\u0000Twenty-eight patients with progressive metastatic or locally advanced radioactive refractory differentiated thyroid cancer and 7 patients with anaplastic thyroid cancer were included and received everolimus 10 mg orally once daily. The primary endpoint was disease control rate [complete (CR) + partial response (PR) + stable disease (SD) > 24 weeks]. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and mutational and pharmacokinetic-related outcomes.\u0000\u0000\u0000Results\u0000Median follow-up duration was 38 months (2-64). Seventeen patients (65%) showed SD, of which 15 (58%) showed SD >24 weeks. No CR or PR was observed. Median PFS and OS were 9 [95% confidence interval (CI): 4 to 14] and 18 (95% CI: 7 to 29) months, respectively. Survival was negatively influenced by the presence of bone metastases. Toxicity was predominantly grade 1/2 and included anemia (64%), cough (64%), stomatitis (61%), and hyperglycemia (61%). Duration of SD was related to everolimus exposure. The presence of somatic gene variants related to mTOR signaling did not clearly stratify for responses.\u0000\u0000\u0000Conclusion\u0000Everolimus has clinically relevant antitumor activity in patients with advanced differentiated thyroid cancer. Given the observed disease control rate and the relatively low toxicity profile, further investigation of everolimus in sequential or combination therapy in these patients is warranted.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"30 1","pages":"698–707"},"PeriodicalIF":0.0,"publicationDate":"2016-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85365100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frida Dalin, Gabriel Nordling Eriksson, P. Dahlqvist, Å. Hallgren, J. Wahlberg, O. Ekwall, S. Söderberg, J. Rönnelid, P. Olcén, O. Winqvist, S. Catrina, B. Kriström, Maria Laudius, M. Isaksson, Maria Halldin Stenlid, J. Gustafsson, G. Gebre-Medhin, S. Björnsdóttir, A. Janson, A. Åkerman, J. Åman, K. Duchén, Ragnhildur Bergthorsdottir, G. Johannsson, E. Lindskog, M. Landin-Olsson, M. Elfving, E. Waldenström, A. Hulting, O. Kämpe, S. Bensing
Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality. Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors. Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008–2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls. Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined. Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.
{"title":"Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study","authors":"Frida Dalin, Gabriel Nordling Eriksson, P. Dahlqvist, Å. Hallgren, J. Wahlberg, O. Ekwall, S. Söderberg, J. Rönnelid, P. Olcén, O. Winqvist, S. Catrina, B. Kriström, Maria Laudius, M. Isaksson, Maria Halldin Stenlid, J. Gustafsson, G. Gebre-Medhin, S. Björnsdóttir, A. Janson, A. Åkerman, J. Åman, K. Duchén, Ragnhildur Bergthorsdottir, G. Johannsson, E. Lindskog, M. Landin-Olsson, M. Elfving, E. Waldenström, A. Hulting, O. Kämpe, S. Bensing","doi":"10.1210/jc.2016-2522","DOIUrl":"https://doi.org/10.1210/jc.2016-2522","url":null,"abstract":"Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality. Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors. Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008–2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls. Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined. Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"314 1","pages":"379–389"},"PeriodicalIF":0.0,"publicationDate":"2016-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80062375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Marotta, Concetta Sciammarella, M. Capasso, A. Testori, C. Pivonello, M. G. Chiofalo, C. Gambardella, M. Grasso, A. Antonino, A. Annunziata, P. Macchia, R. Pivonello, L. Santini, G. Botti, S. Losito, L. Pezzullo, A. Colao, A. Faggiano
Context: Tumor angiogenesis is determined by host genetic background rather than environment. Germline single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) pathway have demonstrated prognostic value in different tumors. Objectives: Our main objective was to test the prognostic value of germline SNPs of the VEGF pathway in nonadvanced differentiated thyroid cancer (DTC). Secondarily, we sought to correlate analyzed SNPs with microvessel density (MVD). Design: Multicenter, retrospective, observational study. Setting: Four referral centers. Patients: Blood samples were obtained from consecutive DTC patients. Genotyping was performed according to the TaqMan protocol, including 4 VEGF-A (−2578C>A, −460T>C, +405G>C, and +936C>T) and 2 VEGFR-2 (+1192 C>T and +1719 T>A) SNPs. MVD was estimated by means of CD34 staining. Outcome Measures: Rate of recurrent structural disease/disease-free survival (DFS). Difference in MVD between tumors from patients with different genotype. Results: Two hundred four patients with stage I–II DTC (mean follow-up, 73 ± 64 months) and 240 patients with low- to intermediate-risk DTC (mean follow-up, 70 ± 60 months) were enrolled. Two “risk” genotypes were identified by combining VEGF-A SNPs −2578 C>A, −460 T>C, and +405 G>C. The ACG homozygous genotype was protective in both stage I–II (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01 to 1.43; P = 0.018) and low- to intermediate-risk (OR, 0.14; 95% CI, 0.01 to 1.13; P = 0.035) patients. The CTG homozygous genotype was significantly associated with recurrence in stage I–II (OR, 5.47; 95% CI, 1.15 to 26.04; P = 0.018) and was slightly deleterious in low- to intermediate-risk (OR, 3.39; 95% CI, 0.8 to 14.33; P = 0.079) patients. MVD of primary tumors from patients harboring a protective genotype was significantly lower (median MVD, 76.5 ± 12.7 and 86.7 ± 27.9, respectively; P = 0.024). Conclusions: Analysis of germline VEGF-A SNPs could empower a prognostic approach to DTC.
{"title":"Germline Polymorphisms of the VEGF Pathway Predict Recurrence in Nonadvanced Differentiated Thyroid Cancer","authors":"V. Marotta, Concetta Sciammarella, M. Capasso, A. Testori, C. Pivonello, M. G. Chiofalo, C. Gambardella, M. Grasso, A. Antonino, A. Annunziata, P. Macchia, R. Pivonello, L. Santini, G. Botti, S. Losito, L. Pezzullo, A. Colao, A. Faggiano","doi":"10.1210/jc.2016-2555","DOIUrl":"https://doi.org/10.1210/jc.2016-2555","url":null,"abstract":"Context: Tumor angiogenesis is determined by host genetic background rather than environment. Germline single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) pathway have demonstrated prognostic value in different tumors. Objectives: Our main objective was to test the prognostic value of germline SNPs of the VEGF pathway in nonadvanced differentiated thyroid cancer (DTC). Secondarily, we sought to correlate analyzed SNPs with microvessel density (MVD). Design: Multicenter, retrospective, observational study. Setting: Four referral centers. Patients: Blood samples were obtained from consecutive DTC patients. Genotyping was performed according to the TaqMan protocol, including 4 VEGF-A (−2578C>A, −460T>C, +405G>C, and +936C>T) and 2 VEGFR-2 (+1192 C>T and +1719 T>A) SNPs. MVD was estimated by means of CD34 staining. Outcome Measures: Rate of recurrent structural disease/disease-free survival (DFS). Difference in MVD between tumors from patients with different genotype. Results: Two hundred four patients with stage I–II DTC (mean follow-up, 73 ± 64 months) and 240 patients with low- to intermediate-risk DTC (mean follow-up, 70 ± 60 months) were enrolled. Two “risk” genotypes were identified by combining VEGF-A SNPs −2578 C>A, −460 T>C, and +405 G>C. The ACG homozygous genotype was protective in both stage I–II (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01 to 1.43; P = 0.018) and low- to intermediate-risk (OR, 0.14; 95% CI, 0.01 to 1.13; P = 0.035) patients. The CTG homozygous genotype was significantly associated with recurrence in stage I–II (OR, 5.47; 95% CI, 1.15 to 26.04; P = 0.018) and was slightly deleterious in low- to intermediate-risk (OR, 3.39; 95% CI, 0.8 to 14.33; P = 0.079) patients. MVD of primary tumors from patients harboring a protective genotype was significantly lower (median MVD, 76.5 ± 12.7 and 86.7 ± 27.9, respectively; P = 0.024). Conclusions: Analysis of germline VEGF-A SNPs could empower a prognostic approach to DTC.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"8 1","pages":"661–671"},"PeriodicalIF":0.0,"publicationDate":"2016-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78909564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Reyes-Umpierrez, Georgia M Davis, Saumeth Cardona, F. Pasquel, Limin Peng, S. Jacobs, P. Vellanki, M. Fayfman, Sonya Haw, Michael E. Halkos, R. Guyton, V. Thourani, G. Umpierrez
Objective We aimed to determine (a) longitudinal changes of inflammatory and oxidative stress markers and (b) the association between markers of inflammation and perioperative complications in coronary artery bypass surgery (CABG) patients treated with intensive vs conservative blood glucose (BG) control. Methods Patients with diabetes (n = 152) and without diabetes with hyperglycemia (n = 150) were randomized to intensive (n = 151; BG: 100-140 mg/dL) or to conservative (n = 151; BG: 141-180 mg/dL) glycemic targets. Plasma cortisol, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α, interleukin-6 (IL-6), thiobarbituric acid-reactive substances, and 2'-7'-dichlorofluorescein were measured prior to and at days 3, 5, and 30 after surgery. Results Intensive glycemic control resulted in lower mean BG (132 ± 14 mg/dL vs 154 ± 17 mg/dL, P < 0.001) in the intensive care unit. Plasma cortisol and inflammatory markers increased significantly from baseline after the third and fifth day of surgery (P < 0.001), and returned to baseline levels at 1 month of follow-up. Patients with perioperative complications had higher levels of cortisol, hsCRP, IL-6, and oxidative stress markers compared with those without complications. There were no significant differences in inflammatory and oxidative stress markers between patients, with or without diabetes or complications, treated with intensive or conventional glucose targets. Conclusion We report no significant differences in circulating markers of acute inflammatory and oxidative stress response in cardiac surgery patients, with or without diabetes, treated with intensive (100-140 mg/dL) or conservative (141-180 mg/dL) insulin regimens.
{"title":"Inflammation and Oxidative Stress in Cardiac Surgery Patients Treated to Intensive Versus Conservative Glucose Targets","authors":"David Reyes-Umpierrez, Georgia M Davis, Saumeth Cardona, F. Pasquel, Limin Peng, S. Jacobs, P. Vellanki, M. Fayfman, Sonya Haw, Michael E. Halkos, R. Guyton, V. Thourani, G. Umpierrez","doi":"10.1210/jc.2016-3197","DOIUrl":"https://doi.org/10.1210/jc.2016-3197","url":null,"abstract":"Objective\u0000We aimed to determine (a) longitudinal changes of inflammatory and oxidative stress markers and (b) the association between markers of inflammation and perioperative complications in coronary artery bypass surgery (CABG) patients treated with intensive vs conservative blood glucose (BG) control.\u0000\u0000\u0000Methods\u0000Patients with diabetes (n = 152) and without diabetes with hyperglycemia (n = 150) were randomized to intensive (n = 151; BG: 100-140 mg/dL) or to conservative (n = 151; BG: 141-180 mg/dL) glycemic targets. Plasma cortisol, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α, interleukin-6 (IL-6), thiobarbituric acid-reactive substances, and 2'-7'-dichlorofluorescein were measured prior to and at days 3, 5, and 30 after surgery.\u0000\u0000\u0000Results\u0000Intensive glycemic control resulted in lower mean BG (132 ± 14 mg/dL vs 154 ± 17 mg/dL, P < 0.001) in the intensive care unit. Plasma cortisol and inflammatory markers increased significantly from baseline after the third and fifth day of surgery (P < 0.001), and returned to baseline levels at 1 month of follow-up. Patients with perioperative complications had higher levels of cortisol, hsCRP, IL-6, and oxidative stress markers compared with those without complications. There were no significant differences in inflammatory and oxidative stress markers between patients, with or without diabetes or complications, treated with intensive or conventional glucose targets.\u0000\u0000\u0000Conclusion\u0000We report no significant differences in circulating markers of acute inflammatory and oxidative stress response in cardiac surgery patients, with or without diabetes, treated with intensive (100-140 mg/dL) or conservative (141-180 mg/dL) insulin regimens.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"115 1","pages":"309–315"},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80627525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenjie Ma, Tao Huang, Y. Heianza, Tiange Wang, Dianjianyi Sun, J. Tong, D. Williamson, G. Bray, F. Sacks, L. Qi
Context Adiponectin plays key roles in regulating appetite and food intake. Objective To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels. Design, Setting, and Participants A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial. Main Outcome Measures Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger. Results Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. Additionally, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P for interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but it was not associated with adiponectin changes in the high-fat group (P = 0.31). Conclusions Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake.
{"title":"Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets","authors":"Wenjie Ma, Tao Huang, Y. Heianza, Tiange Wang, Dianjianyi Sun, J. Tong, D. Williamson, G. Bray, F. Sacks, L. Qi","doi":"10.1210/jc.2016-2909","DOIUrl":"https://doi.org/10.1210/jc.2016-2909","url":null,"abstract":"Context\u0000Adiponectin plays key roles in regulating appetite and food intake.\u0000\u0000\u0000Objective\u0000To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels.\u0000\u0000\u0000Design, Setting, and Participants\u0000A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial.\u0000\u0000\u0000Main Outcome Measures\u0000Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger.\u0000\u0000\u0000Results\u0000Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. Additionally, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P for interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but it was not associated with adiponectin changes in the high-fat group (P = 0.31).\u0000\u0000\u0000Conclusions\u0000Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"82 1","pages":"316–325"},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79957278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Watts, J. Cauley, R. Jackson, A. LaCroix, Cora E. Lewis, J. Manson, J. Neuner, L. Phillips, M. Stefanick, J. Wactawski‐Wende, C. Crandall
Context The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT. Objective The purpose of this study was to examine fractures after discontinuation of HT. Design and Setting Two placebo-controlled randomized trials served as the study setting. Patients Study patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period. Interventions Trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy. Main Outcome Measures Total fractures and hip fractures through 5 years after discontinuation of HT were recorded. Results Hip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03). Conclusions We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.
{"title":"No Increase in Fractures After Stopping Hormone Therapy: Results From the Women’s Health Initiative","authors":"N. Watts, J. Cauley, R. Jackson, A. LaCroix, Cora E. Lewis, J. Manson, J. Neuner, L. Phillips, M. Stefanick, J. Wactawski‐Wende, C. Crandall","doi":"10.1210/jc.2016-3270","DOIUrl":"https://doi.org/10.1210/jc.2016-3270","url":null,"abstract":"Context\u0000The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT.\u0000\u0000\u0000Objective\u0000The purpose of this study was to examine fractures after discontinuation of HT.\u0000\u0000\u0000Design and Setting\u0000Two placebo-controlled randomized trials served as the study setting.\u0000\u0000\u0000Patients\u0000Study patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period.\u0000\u0000\u0000Interventions\u0000Trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy.\u0000\u0000\u0000Main Outcome Measures\u0000Total fractures and hip fractures through 5 years after discontinuation of HT were recorded.\u0000\u0000\u0000Results\u0000Hip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03).\u0000\u0000\u0000Conclusions\u0000We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"31 1","pages":"302–308"},"PeriodicalIF":0.0,"publicationDate":"2016-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78071017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Himika Chawla, S. Saha, D. Kandasamy, Raju Sharma, V. Sreenivas, R. Goswami
Context Bone mineral density (BMD) is increased in idiopathic hypoparathyroidism (IH). Parathyroid hormone (PTH) deficiency, hypocalcemic seizures, and anticonvulsants could compromise skeletal health in IH. Objective We assessed vertebral fractures (VFs) and related factors in IH and change in BMD during follow-up. Design VFs were assessed by morphometry. BMD was assessed by dual-energy X-ray absorptiometery at the lumbar spine, hip, and forearm. Change in BMD was assessed in a subset after a 10-year follow-up. Setting The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Subjects Included were 104 patients with IH and 64 healthy controls. Hypocalcemia, hyperphosphatemia, normal kidney function, and low serum PTH levels were used to diagnose IH. Results VFs were seen in 18.3% of patients with IH and 4.7% of controls (odds ratio, 4.54; 95% confidence interval, 1.28 to 16.04). Use of anticonvulsants and menopause were significantly associated (P < 0.05) with VF. Mean BMD at lumbar spine and hip were higher by 21.4% and 8.6%, respectively, in IH than in controls (P < 0.001), respectively. BMD significantly increased during follow-up at all sites. Change in BMD correlated with maintenance of the serum calcium/phosphorus ratio during follow-up. Conclusions Despite increased BMD, prevalence of vertebral-fractures is greater in patients with IH, especially in postmenopausal women and those on anticonvulsant therapy.
{"title":"Vertebral Fractures and Bone Mineral Density in Patients With Idiopathic Hypoparathyroidism on Long-Term Follow-Up","authors":"Himika Chawla, S. Saha, D. Kandasamy, Raju Sharma, V. Sreenivas, R. Goswami","doi":"10.1210/jc.2016-3292","DOIUrl":"https://doi.org/10.1210/jc.2016-3292","url":null,"abstract":"Context\u0000Bone mineral density (BMD) is increased in idiopathic hypoparathyroidism (IH). Parathyroid hormone (PTH) deficiency, hypocalcemic seizures, and anticonvulsants could compromise skeletal health in IH.\u0000\u0000\u0000Objective\u0000We assessed vertebral fractures (VFs) and related factors in IH and change in BMD during follow-up.\u0000\u0000\u0000Design\u0000VFs were assessed by morphometry. BMD was assessed by dual-energy X-ray absorptiometery at the lumbar spine, hip, and forearm. Change in BMD was assessed in a subset after a 10-year follow-up.\u0000\u0000\u0000Setting\u0000The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India.\u0000\u0000\u0000Subjects\u0000Included were 104 patients with IH and 64 healthy controls. Hypocalcemia, hyperphosphatemia, normal kidney function, and low serum PTH levels were used to diagnose IH.\u0000\u0000\u0000Results\u0000VFs were seen in 18.3% of patients with IH and 4.7% of controls (odds ratio, 4.54; 95% confidence interval, 1.28 to 16.04). Use of anticonvulsants and menopause were significantly associated (P < 0.05) with VF. Mean BMD at lumbar spine and hip were higher by 21.4% and 8.6%, respectively, in IH than in controls (P < 0.001), respectively. BMD significantly increased during follow-up at all sites. Change in BMD correlated with maintenance of the serum calcium/phosphorus ratio during follow-up.\u0000\u0000\u0000Conclusions\u0000Despite increased BMD, prevalence of vertebral-fractures is greater in patients with IH, especially in postmenopausal women and those on anticonvulsant therapy.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"101 1","pages":"251–258"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75453149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Context Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing β-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown. Objective To investigate the PDG compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of β-cells. Design, Setting, and Participants Pancreases from 46 brain dead organ donors (22 with T1D, 24 nondiabetic controls) were investigated for activation (increased proliferation) and markers of pancreatic exocrine and endocrine progenitors. Results PDG cell replication was increased in T1D (6.3% ± 1.6% vs 0.6% ± 0.1%, P < 0.001, T1D vs nondiabetic), most prominently in association with pancreatic inflammation. There were increased progenitor-like cells in PDGs of T1D, but predominantly with an exocrine fate. Conclusion The PDG compartment is activated in T1D consistent with a response to ongoing inflammation, and via resulting ductal hyperplasia may contribute to local obstructive pancreatitis and eventual pancreatic atrophy characteristic of T1D. However, there is no evidence of effective endocrine cell formation from PDGs.
胰管腺(PDGs)已被认为是胰腺外分泌损伤的再生来源，因此可能作为器官干细胞的生态位。有证据表明，长期存在的1型糖尿病(T1D)存在持续的β细胞形成，但其来源尚不清楚。目的研究T1D患者胰腺的PDG隔室是否具有活跃的再生特征(祖细胞的存在和增殖的增加)，特别是作为β细胞的潜在来源。设计、环境和参与者:研究了46例脑死亡器官供体(22例T1D患者，24例非糖尿病对照)的胰腺细胞的激活(增殖增加)和胰腺外分泌和内分泌祖细胞的标志物。结果T1D组spdg细胞复制增加(6.3%±1.6% vs 0.6%±0.1%，P < 0.001, T1D组vs非糖尿病组)，与胰腺炎症相关最为显著。在T1D的PDGs中有增加的祖细胞样细胞，但主要是外分泌的命运。结论PDG间室在T1D中被激活，与持续炎症反应一致，并通过由此产生的导管增生可能导致局部梗阻性胰腺炎和最终的T1D胰腺萎缩特征。然而，没有证据表明PDGs能有效形成内分泌细胞。
{"title":"Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes","authors":"A. Moin, P. Butler, A. Butler","doi":"10.1210/jc.2016-3001","DOIUrl":"https://doi.org/10.1210/jc.2016-3001","url":null,"abstract":"Context\u0000Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing β-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown.\u0000\u0000\u0000Objective\u0000To investigate the PDG compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of β-cells.\u0000\u0000\u0000Design, Setting, and Participants\u0000Pancreases from 46 brain dead organ donors (22 with T1D, 24 nondiabetic controls) were investigated for activation (increased proliferation) and markers of pancreatic exocrine and endocrine progenitors.\u0000\u0000\u0000Results\u0000PDG cell replication was increased in T1D (6.3% ± 1.6% vs 0.6% ± 0.1%, P < 0.001, T1D vs nondiabetic), most prominently in association with pancreatic inflammation. There were increased progenitor-like cells in PDGs of T1D, but predominantly with an exocrine fate.\u0000\u0000\u0000Conclusion\u0000The PDG compartment is activated in T1D consistent with a response to ongoing inflammation, and via resulting ductal hyperplasia may contribute to local obstructive pancreatitis and eventual pancreatic atrophy characteristic of T1D. However, there is no evidence of effective endocrine cell formation from PDGs.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"10 1","pages":"200–209"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82466418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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